3ZG8

Crystal Structure of Penicillin Binding Protein 4 from Listeria monocytogenes in the Ampicillin bound form

3ZG8 の概要

• エントリーDOI: 10.2210/pdb3zg8/pdb
• 関連するPDBエントリー: 3ZG7 3ZG9 3ZGA
• 分子名称: PENICILLIN-BINDING PROTEIN, PENICILLIN-BINDING PROTEIN 4, (2R,4S)-2-[(1R)-1-{[(2R)-2-amino-2-phenylacetyl]amino}-2-oxoethyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid, ... (5 entities in total)
• 機能のキーワード: penicillin-binding protein
• 由来する生物種: LISTERIA MONOCYTOGENES; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63776.81

構造登録者

Jeong, J.H.,Kim, Y.G. (登録日: 2012-12-17, 公開日: 2013-05-29, 最終更新日: 2024-11-06)

主引用文献

Jeong, J.,Kim, Y.,Rojviriya, C.,Ha, S.,Kang, B.S.,Kim, Y.
Crystal Structures of Bifunctional Penicillin-Binding Protein 4 from Listeria Monocytogenes.
Antimicrob.Agents Chemother., 57:3507-, 2013

PubMed Abstract: Penicillin-binding proteins (PBPs), which catalyze the biosynthesis of the peptidoglycan chain of the bacterial cell wall, are the major molecular target of bacterial antibiotics. Here, we present the crystal structures of the bifunctional peptidoglycan glycosyltransferase (GT)/transpeptidase (TP) PBP4 from Listeria monocytogenes in the apo-form and covalently linked to two β-lactam antibiotics, ampicillin and carbenicillin. The orientation of the TP domain with respect to the GT domain is distinct from that observed in the previously reported structures of bifunctional PBPs, suggesting interdomain flexibility. In this structure, the active site of the GT domain is occluded by the close apposition of the linker domain, which supports the hypothesis that interdomain flexibility is related to the regulation of GT activity. The acylated structures reveal the mode of action of β-lactam antibiotics toward the class A PBP4 from the human pathogen L. monocytogenes. Ampicillin and carbenicillin can access the active site and be acylated without requiring a structural rearrangement. In addition, the active site of the TP domain in the apo-form is occupied by the tartrate molecule via extensive hydrogen bond interactions with the catalytically important residues; thus, derivatives of the tartrate molecule may be useful in the search for new antibiotics to inhibit PBPs.

PubMed: 23669378
DOI: 10.1128/AAC.00144-13

実験手法

X-RAY DIFFRACTION (2.094 Å)